The present invention is generally directed to a flexible container or bottle and more particularly relates to apparatus for instilling a medicament into an eye.
A great number of devices have been developed for instilling medicament to an eye. Well known eye drop containers conventionally include a squeezable container and a nozzle for releasing drops of medicament into the eye by compression of the container.
It is well known that such containers must be formed from materials having little or no interaction with the intended contents of the container or bottle both in order to prevent contamination of the contained fluid and the leakage of fluids through the bottle. This selection of container materials is particularly important for drug/pharmaceutical products since changes in a particular drug formulation due to impurities introduced by or through the container wall, and changes in the drug formulation over time due to migration of various components through the container walls can have a profound effect on the products"" performance in both physical and chemical terms.
These effects are commonly observed with flexible containers such as I/V infusion bags and multidose nonpreserved and preserved drug delivery systems. An improper selection of container materials can result in water/weight loss, gas permeability, drug instability and drug absorption and adsorption. The problem, of course, is more acute for flexible or pliable containers designed for the dispensing of formulations contained therein. Most polymers suitable for the construction of flexible containers, such as polyethylene, Kraton, C-Flex, Sarlink, are not suitable due to the absorption or permeation of drug formulations therethrough.
When preservative-free medicaments are utilized, simple eye drop dispensers are not practical because there are no means for preventing the tip from being contaminated due to its exposure to air. Such tip contamination ultimately spreads to the medicament in the container.
In an attempt to overcome these problems, apparatus has been developed for applying a medicament to an eye which includes a nozzle having a seam which is normally in a closed position for preventing the passage of medicament through the nozzle, and which opens in response to a flow of medicament of sufficient pressure to enable opening of the seam in order to permit the passage of medicament through the nozzle for release into the eye, see U.S. Pat. No. 5,685,869.
While this nozzle is suitable, it is necessary to provide a suitable reservoir of medicament in order to create a working, producible device for multiple dose delivery of a preservative-free product of sufficient dose accuracy for consumer benefit and regulatory body registration over an extended period of time of up to six months or more.
Operation of prior art devices such as set forth in the hereinabove referenced U.S. patent, typically causes a small negative pressure, or vacuum, within the medicament container during operation. When a collapsible container is utilized to accommodate shrinking of volume of the medicament reservoir, the materials of construction may not satisfactorily inhibit the permeation of air through the container walls to provide a desired long term use in storage of the device without contamination of the stored medicament.
The present invention overcomes the shortcomings of the prior art devices by providing nozzle and medicament reservoir combination which enables multiple dose delivery of a preservative-free product with accurate dose dispensing over extended periods of time.
Apparatus is provided in accordance with the present invention for, multi-dose delivery of preservative-free pharmaceuticals. Generally, apparatus includes a flexible container which provides a means for holding and maintaining a sterile drug formulation. To achieve this result, the flexible container is formed from a film laminate as hereinafter described in greater detail.
Nozzle means are provided and disposed in fluid communication with the flexible container for dropwise dispensing of the formulation from the flexible container. The nozzle means includes an outer nozzle portion and an inner nozzle portion received within the outer nozzle portion. This combination provides a normally sealed interface therebetween and, importantly, the nozzle portion is sufficiently flexible to enable expansion thereof and passage of drug formulation thereto. The passage of drug formulation occurs when sufficient pressure is provided. This pressure is provided by a piston which forces metered amounts of formulation from the flexible container through the interface.
More particularly, the flexible container includes a film laminate having sufficient flexibility to collapse in volume upon withdrawal of formulation therefrom by""the piston. This prevents any pressure differential occurring across the film laminate which further ensures not only operation of the piston but prevention of any air permeation of the film laminate due to such pressure.
The piston means is sized for releasing a selected volume formulation into an eye. For ease of manufacture, the flexible container in the outer nozzle portion are intricately formed and the piston means is disposed within the flexible container.
Still more particularly, in accordance with the present invention, the film laminate may include a layer of linear load density polyethylene for forming an outside layer of the flexible container, a layer of biaxially oriented nylon for forming a core layer of the flexible container and a layer of linear low density polyethylene for forming an inside layer of the flexible container. The outside and the inside layer are bonded to the core layer by separate layers of polyurethane adhesive.
Further, the film structure may include and outside and inside polyethylene layer with a density of between about 0.91 to about 0.94 g/cm3. Further, the outside layer may include approximately 0.05% to about 0.15% by way of a fatty acid amide containing 8 to 22 carbon atoms. Still more specifically, the fatty acid amide may be an oleic amide.
The outside layer may have a coefficient friction of between about 0.2 to 0.4 and the polyurethane adhesive may comprise a polyestra-urethanediol resin.
In addition, to maintain integrity of the film laminate, the inside and outside layers may be bonded to the core layer where at least 500 gms/inch of force as a delimination strength. Further, to prevent oxidation, the inside low density polyethylene may include an antioxidant, a stabilizer and an anti-blocking agent.